AbstractActivity and pharmacokinetics of a praziquantel crystalline polymorph in the Schistosoma mansoni mouse model.

AbstractActivity and pharmacokinetics of a praziquantel crystalline polymorph in the Schistosoma mansoni mouse model. Eur J Pharm Biopharm. 2019 Jun 29;: Authors: Lombardo FC, Perissutti B, Keiser J Abstract Schistosomiasis is a global disease of significant public health relevance. Only one racemic drug, praziquantel, characterized by low bioavailability low water solubility and extensive first pass metabolism, is currently available. We studied a new praziquantel formulation (polymorph B), which is based on a racemic praziquantel crystalline polymorph (TELCEU01). It's in vitro activity was tested on newly transformed schistosomula (NTS) and adult Schistosoma mansoni In vivo studies were conducted in mice harboring chronic S. mansoni infections. Pharmacokinetic PK profiles of R- and S-praziquantel and R- S- polymorph B following oral administration with both formulations were generated by sampling mice at 30, 60, 240 min and 24 hours post-treatment, followed by LC-MS/MS analysis. PK parameters were calculated using a non-compartmental analysis with a linear trapezoidal model. In vitro, commercial praziquantel and the polymorph B performed similarly on both NTS (IC50 = 2.58 and 2.40 µg/mL at 72 h) and adults (IC50 = 0.05 and 0.07 µg/mL at 72 h). Praziquantel showed higher in vivo efficacy with an ED50 of 58.75 mg/kg compared to an ED50 of 122.61 mg/kg for the polymorph B. The PK profiles of the two drugs exhibited differences: R-pr...
Source: European Journal of Pharmaceutics and Biopharmaceutics - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharm Biopharm Source Type: research